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      Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?

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          Abstract

          Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.

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          Most cited references127

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          Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab

          Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma (MM) but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity.
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            A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

            There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.
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              The microbiome, cancer, and cancer therapy

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                17 September 2019
                September 2019
                : 20
                : 18
                : 4584
                Affiliations
                [1 ]Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH) UMR 1071 Inserm/Université Clermont Auvergne, USC-INRA 2018, CRNH Auvergne, F-63000 Clermont-Ferrand, France; amelie.lopes0703@ 123456gmail.com (A.L.); guillaume.carrier@ 123456icm.unicancer.fr (G.C.); jveziant@ 123456chu-clermontferrand.fr (J.V.); elisabeth.billard@ 123456uca.fr (E.B.); nicolas.barnich@ 123456uca.fr (N.B.); jgagniere@ 123456chu-clermontferrand.fr (J.G.); Emilie.VAZEILLE@ 123456uca.fr (E.V.); mathilde.bonnet@ 123456uca.fr (M.B.)
                [2 ]Biologics Research, Sanofi R&D, 94400 Vitry-Sur-Seine, France
                [3 ]Surgical Oncology Department, Institut du Cancer de Montpellier (ICM), Univ Montpellier, 34298 Montpellier, France
                [4 ]Service de Chirurgie Digestive, CHU Clermont-Ferrand, Inserm, Université Clermont Auvergne, 63003 Clermont-Ferrand, France
                [5 ]3iHP, CHU Clermont-Ferrand, Inserm, Université Clermont Auvergne, 63003 Clermont-Ferrand, France
                [6 ]Service d’Hépato-gastro-entérologie, CHU Clermont-Ferrand, Inserm, Université Clermont Auvergne, 63003 Clermont-Ferrand, France
                Author notes
                [* ]Correspondence: romain.villeger@ 123456uca.fr
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-2815-045X
                https://orcid.org/0000-0001-8959-7840
                https://orcid.org/0000-0002-1547-1054
                https://orcid.org/0000-0002-6066-4584
                https://orcid.org/0000-0001-9465-7844
                https://orcid.org/0000-0003-3629-7267
                Article
                ijms-20-04584
                10.3390/ijms20184584
                6770123
                31533218
                7c9a265a-41ef-423f-b277-1d43a492124c
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 August 2019
                : 13 September 2019
                Categories
                Review

                Molecular biology
                intestinal microbiota,chemotherapy,probiotics,cancer,radiotherapy,anticancer treatment,surgery,microbiome,adjuvant therapies

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